Dataset Information

Colicin E2 Expression in Lactobacillus brevis DT24, A Vaginal Probiotic Isolate, against Uropathogenic Escherichia coli.

ABSTRACT: Novel therapeutic approaches are needed to combat the urinary tract infection in women. During menstruation elevated protein concentration and increase in oxygen and carbon dioxide concentrations with decrease in vaginal Lactobacilli all together contribute to urinary tract infections. Lactobacillus species are a predominant member of the vaginal microflora and are critical in the prevention of a number of urogenital diseases. In order to increase antimicrobial potential of vaginal Lactobacilli, bacteriocin colicin E2 which has specific activity against uropathogenic Escherichia coli has been overexpressed in vaginal probiotic Lactobacillus brevis DT24. Recombinant Lactobacillus brevis DT24 expressing colicin E2 showed much higher inhibitory activity against uropathogenic Escherichia coli than wild type L. brevis DT24 in vitro. Efficacy of probiotic Lactobacillus brevis DT24 expressing colicin E2 protein is required for further in vivo evaluation.

SUBMITTER: Trivedi D

PROVIDER: S-EPMC3932652 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Colicin E2 Expression in Lactobacillus brevis DT24, A Vaginal Probiotic Isolate, against Uropathogenic Escherichia coli.

Trivedi Disha D Jena Prasant Kumar PK Seshadri Sriram S

ISRN urology 20140204

Novel therapeutic approaches are needed to combat the urinary tract infection in women. During menstruation elevated protein concentration and increase in oxygen and carbon dioxide concentrations with decrease in vaginal Lactobacilli all together contribute to urinary tract infections. Lactobacillus species are a predominant member of the vaginal microflora and are critical in the prevention of a number of urogenital diseases. In order to increase antimicrobial potential of vaginal Lactobacilli, ...[more]

PMID: 24649377

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Project description:The outer membrane of Gram-negative bacteria presents a significant barrier for molecules entering the cell. Nevertheless, colicins, which are antimicrobial proteins secreted by Escherichia coli, can target other E. coli cells by binding to cell surface receptor proteins and activating their import, resulting in cell death. Previous studies have documented high rates of nonspecific resistance (insensitivity) of various E. coli strains toward colicins that is independent of colicin-specific immunity and is instead associated with lipopolysaccharide (LPS) in the outer membrane. This observation poses a contradiction: why do E. coli strains have colicin-expressing plasmids, which are energetically costly to retain, if cells around them are likely to be naturally insensitive to the colicin they produce? Here, using a combination of transposon sequencing and phenotypic microarrays, we show that colicin insensitivity of uropathogenic E. coli sequence type 131 (ST131) is dependent on the production of its O-antigen but that minor changes in growth conditions render the organism sensitive toward colicins. The reintroduction of O-antigen into E. coli K-12 demonstrated that it is the density of O-antigen that is the dominant factor governing colicin insensitivity. We also show, by microscopy of fluorescently labelled colicins, that growth conditions affect the degree of occlusion by O-antigen of outer membrane receptors but not the clustered organization of receptors. The result of our study demonstrate that environmental conditions play a critical role in sensitizing E. coli toward colicins and that O-antigen in LPS is central to this role.IMPORTANCE Escherichia coli infections can be a major health burden, especially with the organism becoming increasingly resistant to "last-resort" antibiotics such as carbapenems. Although colicins are potent narrow-spectrum antimicrobials with potential as future antibiotics, high levels of naturally occurring colicin insensitivity have been documented which could limit their efficacy. We identify O-antigen-dependent colicin insensitivity in a clinically relevant uropathogenic E. coli strain and show that this insensitivity can be circumvented by minor changes to growth conditions. The results of our study suggest that colicin insensitivity among E. coli organisms has been greatly overestimated, and as a consequence, colicins could in fact be effective species-specific antimicrobials targeting pathogenic E. coli such as uropathogenic E. coli (UPEC).

Project description:Post-transcriptional regulation of gene expression plays a crucial role in many bacterial pathways. In particular, the translation of mRNA can be regulated by trans-acting, small, non-coding RNAs (sRNAs) or mRNA-binding proteins, each of which has been successfully treated theoretically using two-component models. An important system that includes a combination of these modes of post-transcriptional regulation is the Colicin E2 system. DNA damage, by triggering the SOS response, leads to the heterogeneous expression of the Colicin E2 operon including the cea gene encoding the toxin colicin E2, and the cel gene that codes for the induction of cell lysis and release of colicin. Although previous studies have uncovered the system's basic regulatory interactions, its dynamical behavior is still unknown. Here, we develop a simple, yet comprehensive, mathematical model of the colicin E2 regulatory network, and study its dynamics. Its post-transcriptional regulation can be reduced to three hierarchically ordered components: the mRNA including the cel gene, the mRNA-binding protein CsrA, and an effective sRNA that regulates CsrA. We demonstrate that the stationary state of this system exhibits a pronounced threshold in the abundance of free mRNA. As post-transcriptional regulation is known to be noisy, we performed a detailed stochastic analysis, and found fluctuations to be largest at production rates close to the threshold. The magnitude of fluctuations can be tuned by the rate of production of the sRNA. To study the dynamics in response to an SOS signal, we incorporated the LexA-RecA SOS response network into our model. We found that CsrA regulation filtered out short-lived activation peaks and caused a delay in lysis gene expression for prolonged SOS signals, which is also seen in experiments. Moreover, we showed that a stochastic SOS signal creates a broad lysis time distribution. Our model thus theoretically describes Colicin E2 expression dynamics in detail and reveals the importance of the specific regulatory components for the timing of toxin release.

Dataset Information

Colicin E2 Expression in Lactobacillus brevis DT24, A Vaginal Probiotic Isolate, against Uropathogenic Escherichia coli.

Publications

Colicin E2 Expression in Lactobacillus brevis DT24, A Vaginal Probiotic Isolate, against Uropathogenic Escherichia coli.

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